miR-486-3p通过调控血小板衍生生长因子相关蛋白1抑制卵巢癌细胞增殖的研究

Inhibition of proliferation of ovarian cancer cells by regulation of platelet-derived growth factor-associated protein 1 by miR-486-3p

目的探讨miR-486-3p和血小板衍生生长因子相关蛋白1(platelet-derived growth factor-associated protein 1, PDAP 1)基因在卵巢癌中的表达情况以及它们的相互调控关系。方法回顾性分析2015~2017年在广东医科大学第一附属医院住院并经临床和病理证实为卵巢癌的8例患者临床卵巢癌肿瘤组织标本,收集同期4例卵巢非恶性病变者(阴性对照组)的标本,通过荧光实时定量PCR和免疫印迹技术,分析miR-486-3p和PDAP 1在卵巢癌的表达情况。采用生物信息学和双荧光素酶实验证实它们之间的调控关系,并研究它们对卵巢癌细胞增殖的影响。结果 miR-486-3p在卵巢癌细胞和肿瘤组织中均出现显著下调(P<0.05),而PDAP 1则过表达(P<0.05)。它们的表达量间呈负相关关系(r=-0.82,P<0.05),进一步研究证实PDAP 1是miR-486-3p的靶点。上调miR-486-3p或抑制PDAP 1的表达均可导致卵巢癌细胞增殖受抑。结论以miR-486-3p和PDAP 1为靶点的基因治疗有望应用于卵巢癌治疗。

Objective To clarify the expression and interaction of miR-486-3 p and PDAP 1 gene in ovarian cancer. Methods Retrospective analyzed the tumor tissue specimens from 8 patients who were hospitalized in Affiliated Hospital of Guangdong Medical University and clinically and pathologically confirmed as ovarian cancer in 2015~2017, and collected specimens of 4 patients with non-maglignant ovarian cancer(negative control group).The expression of miR-486-3 p and PDAP 1 in ovarian cancer was analyzed by real-time quantitative PCR and western blotting. Bioinformatics and dual luciferase assays were used to confirm their regulatory relationships. The impact on the proliferation of ovarian cancer cells of miR-486-3 p and PDAP 1 were further investigated. Results MiR-486-3 p was significantly down-regulated in ovarian cancer cells and tumor tissues(P<0.05), whereas PDAP 1 was over-expressed(P<0.05). There was a negative correlation between their expressions. Further studies confirmed that PDAP 1 is the target of miR-486-3 p. Up-regulation of miR-486-3 p or inhibition of PDAP 1 expression can lead to suppressed proliferation of ovarian cancer cells. Conclusion Gene therapy targeting miR-486-3 p and PDAP 1 is expected to be used for the treatment of ovarian cancer.